Respiratory Viral Infections in Patients With Cancer or Undergoing Hematopoietic Cell Transplant

Survival rates for pediatric cancer have steadily improved over time but it remains a significant cause of morbidity and mortality among children. Infections are a major complication of cancer and its treatment. Community acquired respiratory viral infections (CRV) in these patients increase morbidity, mortality and can lead to delay in chemotherapy. These are the result of infections with a heterogeneous group of viruses including RNA viruses, such as respiratory syncytial virus (RSV), influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (HMPV), rhinovirus (RhV), and coronavirus (CoV). These infections maintain a similar seasonal pattern to those of immunocompetent patients. Clinical manifestations vary significantly depending on the type of virus and the type and degree of immunosuppression, ranging from asymptomatic or mild disease to rapidly progressive fatal pneumonia Infections in this population are characterized by a high rate of progression from upper to lower respiratory tract infection and prolonged viral shedding. Use of corticosteroids and immunosuppressive therapy are risk factors for severe disease. The clinical course is often difficult to predict, and clinical signs are unreliable. Accurate prognostic viral and immune markers, which have become part of the standard of care for systemic viral infections, are currently lacking; and management of CRV infections remains controversial. Defining effective prophylactic and therapeutic strategies is challenging, especially considering, the spectrum of immunocompromised patients, the variety of respiratory viruses, and the presence of other opportunistic infections and medical problems. Prevention remains one of the most important strategies against these viruses. Early diagnosis, supportive care and antivirals at an early stage, when available and indicated, have proven beneficial. However, with the exception of neuraminidase inhibitors for influenza infection, there are no accepted treatments. In high-risk patients, pre-emptive treatment with antivirals for upper respiratory tract infection (URTI) to decrease progression to LRTI is a common strategy. In the future, viral load and immune markers may prove beneficial in predicting severe disease, supporting decision making and monitor treatment in this population

Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65.

Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis

Entanglement Entropy from a Holographic Viewpoint

The entanglement entropy has been historically studied by many authors in order to obtain quantum mechanical interpretations of the gravitational entropy. The discovery of AdS/CFT correspondence leads to the idea of holographic entanglement entropy, which is a clear solution to this important problem in gravity. In this article, we would like to give a quick survey of recent progresses on the holographic entanglement entropy. We focus on its gravitational aspects, so that it is comprehensible to those who are familiar with general relativity and basics of quantum field theory.Comment: Latex, 30 pages, invited review for Classical and Quantum Gravity, minor correction

SARS-CoV-2 infection in high-risk children following tixagevimab–cilgavimab (Evusheld) pre-exposure prophylaxis: a single-center observational study

From 8 December 2021 to 26 January 2023, tixagevimab–cilgavimab (T-C) was authorized for pre-exposure prophylaxis of COVID-19. During this period, we used a multidisciplinary team to communicate, screen, approach, and administer T-C to eligible patients. Twenty-seven patients were eligible. Of these, 24 (88.9%) received at least one dose of T-C and three patients received two doses. Majority of patients were White, non-Hispanic, and women. Only two patients had COVID-19 prior to receiving T-C. Seventeen (70.8%) had received two or more doses of SARS-CoV-2 vaccine. No serious adverse events were noted. Seven patients developed SARS-CoV-2 infection within 180 days of receiving T-C (median 102 days; range 28–135), and only one patient developed severe COVID-19 requiring intensive mechanical ventilation in the intensive care unit

Influenza Virus A Infection of Human Monocyte and Macrophage Subpopulations Reveals Increased Susceptibility Associated with Cell Differentiation

Influenza virus infection accounts for significant morbidity and mortality world-wide. Interactions of the virus with host cells, particularly those of the macrophage lineage, are thought to contribute to various pathological changes associated with poor patient outcome. Development of new strategies to treat disease therefore requires a detailed understanding of the impact of virus infection upon cellular responses. Here we report that human blood-derived monocytes could be readily infected with the H3N2 influenza virus A/Udorn/72 (Udorn), irrespective of their phenotype (CD14++/CD16−, CD14++/CD16+ or CD14dimCD16++), as determined by multi-colour flow cytometry for viral haemagglutinin (HA) expression and cell surface markers 8–16 hours post infection. Monocytes are relatively resistant to influenza-induced cell death early in infection, as approximately 20% of cells showed influenza-induced caspase-dependent apoptosis. Infection of monocytes with Udorn also induced the release of IL-6, IL-8, TNFα and IP-10, suggesting that NS1 protein of Udorn does not (effectively) inhibit this host defence response in human monocytes. Comparative analysis of human monocyte-derived macrophages (Mph) demonstrated greater susceptibility to human influenza virus than monocytes, with the majority of both pro-inflammatory Mph1 and anti-inflammatory/regulatory Mph2 cells expressing viral HA after infection with Udorn. Influenza infection of macrophages also induced cytokine and chemokine production. However, both Mph1 and Mph2 phenotypes released comparable amounts of TNFα, IL-12p40 and IP-10 after infection with H3N2, in marked contrast to differential responses to LPS-stimulation. In addition, we found that influenza virus infection augmented the capacity of poorly phagocytic Mph1 cells to phagocytose apoptotic cells by a mechanism that was independent of either IL-10 or the Mer receptor tyrosine kinase/Protein S pathway. In summary, our data reveal that influenza virus infection of human macrophages causes functional alterations that may impact on the process of resolution of inflammation, with implications for viral clearance and lung pathology

An Integrated Transcriptomic and Meta-Analysis of Hepatoma Cells Reveals Factors That Influence Susceptibility to HCV Infection

Hepatitis C virus (HCV) is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc) systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies

Search for high-mass diboson resonances with boson-tagged jets in proton-proton collisions at √s=8 TeV with the ATLAS detector

A search is performed for narrow resonances decaying into WW, WZ, or ZZ boson pairs using 20.3 fb−1 of proton-proton collision data at a centre-of-mass energy of √s=8 TeV recorded with the ATLAS detector at the Large Hadron Collider. Diboson resonances with masses in the range from 1.3 to 3.0 TeV are sought after using the invariant mass distribution of dijets where both jets are tagged as a boson jet, compatible with a highly boosted W or Z boson decaying to quarks, using jet mass and substructure properties. The largest deviation from a smoothly falling background in the observed dijet invariant mass distribution occurs around 2 TeV in the WZ channel, with a global significance of 2.5 standard deviations. Exclusion limits at the 95% confidence level are set on the production cross section times branching ratio for the WZ final state of a new heavy gauge boson, W′, and for the WW and ZZ final states of Kaluza-Klein excitations of the graviton in a bulk Randall-Sundrum model, as a function of the resonance mass. W′ bosons with couplings predicted by the extended gauge model in the mass range from 1.3 to 1.5 TeV are excluded at 95% confidence level

Search for heavy resonances decaying into WW in the eνμν eνμν final state in pp collisions at √s=13 TeV with the ATLAS detector

A search for neutral heavy resonances is performed in the WW→eνμν decay channel using pp collision data corresponding to an integrated luminosity of 36.1fb−1, collected at a centre-of-mass energy of 13TeV by the ATLAS detector at the Large Hadron Collider. No evidence of such heavy resonances is found. In the search for production via the quark–antiquark annihilation or gluon–gluon fusion process, upper limits on σX×B(X→WW) as a function of the resonance mass are obtained in the mass range between 200GeV GeV and up to 5TeV for various benchmark models: a Higgs-like scalar in different width scenarios, a two-Higgs-doublet model, a heavy vector triplet model, and a warped extra dimensions model. In the vector-boson fusion process, constraints are also obtained on these resonances, as well as on a Higgs boson in the Georgi–Machacek model and a heavy tensor particle coupling only to gauge bosons

Search for low-scale gravity signatures in multi-jet final states with the ATLAS detector at √s=8 TeV

A search for evidence of physics beyond the Standard Model in final states with multiple high-transverse-momentum jets is performed using 20.3 fb−1 of proton-proton collision data at √s=8 TeV recorded by the ATLAS detector at the LHC. No significant excess of events beyond Standard Model expectations is observed, and upper limits on the visible cross sections for non-Standard Model production of multi-jet final states are set. A wide variety of models for black hole and string ball production and decay are considered, and the upper limit on the cross section times acceptance is as low as 0.16 fb at the 95% confidence level. For these models, excluded regions are also given as function of the main model parameters

Search for W W/W Z resonance production in ℓνqq final states in pp collisions at √s=13 TeV with the ATLAS detector

A search is conducted for new resonances decaying into a W W or W Z boson pair, where one W boson decays leptonically and the other W or Z boson decays hadronically. It is based on proton-proton collision data with an integrated luminosity of 36.1 fb −1 collected with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of s=13 TeV in 2015 and 2016. The search is sensitive to diboson resonance production via vector-boson fusion as well as quark-antiquark annihilation and gluon-gluon fusion mechanisms. No significant excess of events is observed with respect to the Standard Model backgrounds. Several benchmark models are used to interpret the results. Limits on the production cross section are set for a new narrow scalar resonance, a new heavy vector-boson and a spin-2 Kaluza-Klein graviton.[Figure not available: see fulltext.]